The Latest Research from the 2025 AACR Special Conference

University of Liverpool Faculty of Health & Life Sciences; Flickr

Global researchers convened in Boston, Massachusetts at the annual AACR Special Conference in Cancer Research: Advances in Pancreatic Cancer Research to share the latest updates.  

The conference, subtitled Emerging Science Driving Transformative Solutions, was held from September 28th to October 1st. It showcased some of the most important cutting-edge research on the biology, early detection, interception, and treatment of pancreatic cancer. Now in its 11th year, this important meeting continues to attract hundreds of global leaders across disciplines. This year’s conference included basic, translational, and clinical research, with topics such as tumor evolution, therapeutic resistance, the immunosuppressive tumor microenvironment, cancer metabolism, and emerging immunotherapy strategies rounding out the program. It’s clear that progress is indeed being made in bettering our understanding of pancreatic cancer. This will undoubtedly lead to improved outcomes for more patients. As always, Let’s Win is sharing with you a few of the highlights from this important conference. And we will cover some of these findings and others in more detail in the months to come.

A Potential New Test

Brian M. Wolpin, M.D., M.P.H., director of the Gastrointestinal Cancer Treatment Center at Dana-Farber Cancer Institute in Boston, delivered an opening keynote address titled “Altered Pancreas Function for Detection and Interception of Localized Pancreatic Cancer.” Wolpin focused on the need to find pancreatic cancer earlier, or to intercept it before it develops, given that more than 80 percent of patients are diagnosed with advanced disease.

His talk centered on new strategies for detecting and intercepting localized pancreatic cancer by looking at the altered function of the pancreas. The goal of this research is to create a non-invasive, affordable, and easy-to-use screening tool for high-risk populations. The Wolpin–Nowak Lab is collaborating with cancer centers nationwide to collect data from patients with pancreatic cancer. This includes stool samples, genetic mutation data, imaging tests, and medical records. By analyzing these samples, researchers aim to find genetic and microbial “signatures” that indicate the presence of pancreatic cancer in its early stages. Promising biomarkers in stool that are being investigated for pancreatic cancer include microbiome signatures found in the stool of patients with pancreatic cancer as well as genetic mutations like KRAS and abnormal DNA methylation patterns in genes like BMP3 and NDRG4 in tumor-derived cells shed into the stool.

The Power of AI

Elliot K. Fishman, M.D., of Johns Hopkins Medicine in Baltimore, Maryland, recapped his multidisciplinary team’s research focusing on machine learning and AI to develop tools for automated detection of pancreatic cancer. There is considerable data showing that models can segment the pancreas and identify small tumors, especially those missed by radiologists. Adding advanced tools like cinematic rendering and radiomics improves the process. Currently, about 40 percent of pancreatic tumors under 2 cm are missed in abdominal CT scans, with a 3 to 4 percent error rate overall. Cutting the number of misses in half could potentially save 15,000 lives. The team is also using the ability of AI to predict the etiology and aggressiveness of cystic pancreatic lesions, some of which can lead to the development of pancreatic cancer. A paper will be published in the journal Cancer Discovery shortly, and Let’s Win will be sure to cover it.

KRAS Drug Development

David S. Hong, M.D., of the University of Texas MD Anderson Cancer Center in Houston,  spoke about the progress and potential of KRAS inhibitors in his talk “KRAcking Open KRAS: Thoughts on KRAS Drug Development.” Once thought “undruggable,” KRAS inhibitors are now the focus of numerous clinical trials. Research is still in the infancy of drug development, but in coming years that pace will accelerate. Hong emphasized that learning from every patient is vital and cited the Conquering KRAS in Pancreatic Cancer project, a collaborative research initiative led by the Lustgarten Foundation in partnership with Break Through Cancer, a foundation advancing cross-institutional research in difficult-to-treat cancers.

This initiative focuses on accelerating discovery in pancreatic cancer research by zeroing in on inhibition of RAS in pancreatic cancer. The Lustgarten co-funded team will analyze patient blood and tumor tissue samples from a dedicated collaboration cohort within a clinical trial evaluating daraxonrasib (developed by Revolution Medicines) in patients with pancreatic cancer, using advanced multi-omic and spatial profiling approaches to search for biomarkers able to predict tumor response and how cancer cells adapt to the therapy. In studying these biomarkers, researchers aim to define the biology of drug resistance and potential opportunities for combination drug strategies that may delay or overcome resistance. Let’s Win has covered daraxonrasib; you can read more about those trials on our site.

Cryptic Antigens—Finding New Targets with T Cell Receptor Therapy

William Freed-Pastor, M.D., Ph.D., of the Dana-Farber Cancer Institute spoke about the hunt for mutations in pancreatic cancer that can be targets for immunotherapy and vaccines. Freed-Pastor’s lab at Dana-Farber is researching cryptic antigens, which are peptides from non-coding regions of DNA that can trigger a T cell response against cancer cells, and their potential role in the “dark proteome”—the collection of proteins whose function is not yet well understood.  Their work focuses on identifying these cancer-specific cryptic peptides, particularly in pancreatic cancer, and exploring how to develop new immunotherapies like cancer vaccines or T cell therapies to target them. 

The immune-suppressive environment and low mutational burden in pancreatic tumors have meant that immunotherapy has been thought of as a “fool’s errand” for treatment. But vaccines can indeed induce tumor-specific immune responses as can T cell receptor (TCR) therapies. TCR-based therapies are engineered cell therapies that modify a patient’s own T cells in a lab to recognize and kill cancer cells. The T cells are genetically engineered to express a TCR that can target specific antigens found on tumors. These modified T cells are then infused back into the patient, allowing them to circulate and attack the cancer cells throughout the body.

This approach is particularly promising for solid tumors because it can target intracellular proteins and has shown success in clinical trials. TCR-modified T cells have induced clinical responses even in metastatic disease. Dr. Freed-Pastor’s lab is also beginning to work on a vaccine targeting some of the cryptic antigens, which could help stimulate patients’ T cells to attack tumors expressing those antigens. Such a vaccine could include a collection of the antigens identified in this study, including those frequently found in multiple patients.

Alternating Regimens

A study alternating treatment with NALIRIFOX and gemcitabine plus nab-paclitaxel on a monthly basis is exploring a novel approach by combining two effective chemotherapy regimens in a rotating schedule. The aim of this study, dubbed AltCAP, is to potentially enhance long-term efficacy and manage toxicity. By alternating between the two regimens, the study is trying to leverage the benefits of each while potentially mitigating the side effects associated with a single, consistent therapy. 

This phase II clinical trial is looking at this approach as a first-line treatment for metastatic pancreatic cancer. NALIRIFOX and gemcitabine plus nab-paclitaxel are both established chemotherapy regimens for metastatic pancreatic cancer, with NALIRIFOX having demonstrated an overall survival advantage in the NAPOLI-3 trial.